Potassium Phosphate, Tribasic → {4-[5-({6,6-Dimethyl-4H,6H,7H-pyrazolo[3,2-c][1,4]oxazin-2-yl}amino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl]-2-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}pyridin-3-yl}methyl Acetate

HRID 593170Notes

Reaction equation

HRID 593170 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:21]=[C:14]3[CH2:15][O:16][C:17]([CH3:20])([CH3:19])[CH2:18][N:13]3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1.[C:22]([O:25][CH2:26][C:27]1[C:28]([N:42]2[CH2:53][CH2:52][C:51]3[C:50]4[CH2:49][C:48]([CH3:55])([CH3:54])[CH2:47][C:46]=4[S:45][C:44]=3[C:43]2=[O:56])=[N:29][CH:30]=[CH:31][C:32]=1B1OC(C)(C)C(C)(C)O1)(=[O:24])[CH3:23].C([O-])(=O)C.[Na+].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.C(#N)C>[C:22]([O:25][CH2:26][C:27]1[C:28]([N:42]2[CH2:53][CH2:52][C:51]3[C:50]4[CH2:49][C:48]([CH3:55])([CH3:54])[CH2:47][C:46]=4[S:45][C:44]=3[C:43]2=[O:56])=[N:29][CH:30]=[CH:31][C:32]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:21]=[C:14]3[N:13]([N:12]=2)[CH2:18][C:17]([CH3:20])([CH3:19])[O:16][CH2:15]3)[C:5](=[O:9])[N:6]([CH3:8])[N:7]=1)(=[O:24])[CH3:23]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517045Sodium AcetateHCID 86684597(2-{4,4-Dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl AcetateHCID 866845996-Chloro-4-(6,6-dimethyl-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-2-methylpyridazin-3(2H)-one

Product 1

HCID 86684598{4-[5-({6,6-Dimethyl-4H,6H,7H-pyrazolo[3,2-c][1,4]oxazin-2-yl}amino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl]-2-{4,4-dimethyl-9-oxo-7-thia-10-azatricyclo[6.4.0.02,6]dodeca-1(8),2(6)-dien-10-yl}pyridin-3-yl}methyl AcetateYield 25%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
95 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 330h (133 mg, 0.43 mmol), 330c (178 mg, 0.43 mmol), sodium acetate (71 mg, 0.86 mmol), K3PO4 (182 mg, 0.86 mmol), Pd(dppf)Cl2 (35 mg, 0.043 mmol), acetonitrile (15 mL), and water (0.5 mL). After bubbling nitrogen through the resulting mixture for 20 minutes, the reaction mixture was heated at 95° C. for 3 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was purified with silica-gel column chromatography eluting with 30:1 dichloromethane/methanol to afford 330i as a yellow solid (69 mg, 25%). MS-ESI: [M+H]+ 644.3.

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. customAfter bubbling nitrogen through the resulting mixture for 20 minutes
  4. temperatureAfter this time the reaction was cooled to room temperature
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customThe residue was purified with silica-gel column chromatography
  8. washeluting with 30:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-cdcbd79d61d64769abdac9690b346419
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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